The Biology of . . . Hair

Zeroing in on the molecular switches that regulate hair growth

The scalp is a small city populated by 150,000 individuals whose subcutaneous lives are only dimly comprehensible to us, whom they affect so much. The hair we see, fuss over, curse, write lyrics about, is just dead stuff, pushed up and out of the skin by the follicles below. It is those follicles that are alive, and that drive the growth and shedding we see. "The hair follicle is the only organ that regenerates in the adult in a cyclical way," says Bruno Bernard, head of hair biology research at L'Oréal, the French cosmetics manufacturer. "It is unique." In our follicles, cells still converse in the molecular language of the embryo; in our follicles we remain forever young. Most of us. In some of our follicles. And, of course, forever is a bit of journalistic license.

For a long time most research focused on the dead part of hairon understanding the physics and chemistry of the hair fiber with a view toward designing better shampoos, dyes, and perming agents. But recently the molecular biology revolution has come to the living follicle. In particular, says dermatologist Ralf Paus of the University of Hamburg in Germany, the ability to mutate or knock out certain genes in mice and to see what a mess that makes of their hair has allowed biologists to start picking apart the molecular clockwork that regulates follicle growthwith the ultimate goal of learning how to switch hair growth on and off. "There has been a huge technological advance," Paus says, "and that has made hair research so much more fun and so much more instructive than in all the decades before."

To be sure, those earlier decades of research revealed the outlines of how hair grows. A hair follicle forms in the embryowe are born with all the follicles we'll ever havewhen the epidermis folds down into the underlying connective tissue, or dermis. The narrow pocket that results is filled with three concentric cylinders of epidermal cells; two root sheaths surround the hair shaft itself. At its base, which in growing adult hair is about a sixth of an inch below the skin's surface, the hair shaft envelops a little upraised nubbin of connective tissue called the dermal papilla. Hair grows right there, at the basenot at the tip, the way a plant does.

Around and just above the dermal papilla, cells divide rapidly. As they are pushed upward by the swelling population underneath them, they make keratin, a helical protein. Four keratin helices twist around one another to form a protofibril. Eleven protofibrils form a cable called a microfibril, the microfibrils are bundled together into macrofibrils, and a bundle of macrofibrils fills each hair cell. By the time the cell has moved a fiftieth of an inch upward from the dermal papilla, it is so choked with keratin fibers that it is no longer exchanging material with its environment. That is, it is dead well before it even hits air.

An individual hair typically grows for about three years, at a bit less than half an inch a month. So the maximum length a hair can reach is around a foot and a half. Obviously there are lots of atypical people. When the growth phase ends, the follicle rapidly shrivels and shrinks up toward the surface of the skin; within three weeks the hair's root is only a fiftieth of an inch deep. It now enters a rest phase of about three months in which a comb or even a stiff breeze will rip it out. Then, miraculously, the whole cycle begins again. The follicle grows back down into the skin, renews contact with the dermal papilla, and starts producing a new hair.

Even more miraculous, the 100,000 to 150,000 follicles on your head are all cycling through these phases completely independent of one another. And that's a good thing: If the follicles were synchronized, our hairs would all fall out at the same time, and we would molt. Instead each individual follicle seems to have its own internal clock that drives it from growth to regression and back again. "We still have no clear idea whatsoever of what this molecular clock is," Paus says. "But it is fundamentally important to find out, because if we want to change hair growth in humans, it would be the ideal target."

In some people, you see, the follicle clock runs faster. For 14 years in the 1980s and 1990s, researchers at L'Oréal tracked 10 men month by month, shaving a square centimeter of their scalp and then watching to see how many of the 200 to 300 hairs in that patch grew back. They found, not too surprisingly, that in men with incipient baldness, the average growth phase is shorter. Because a follicle probably has only a limited number of cycles in ita good guess is around 25the shorter the cycle, the sooner it will stop producing hair. That's what happens in most bald men: Their follicles live fast and die young.

Male-pattern baldness, as well as the more diffuse hair loss that some women suffer, are both caused ultimately by dihydrotestosterone (DHT), a metabolite of testosterone. DHT seems like a good idea in youth: It puts hair on male chests and faces, converting follicles that produced only peach fuzz, or "vellus" hair, into ones that produce the "terminal" he-man stuff. But for reasons that remain obscure, DHT has the opposite effect on some follicles of the adult scalp, presumably the ones that are genetically programmed to have more receptors for it. Finasteride, the big success story in the battle against baldness (Merck markets it as Propecia), works by blocking the enzyme that converts testosterone into DHT. In most cases, when men remember to take their pill every day, it stems the advancing tide of hairlessness; in some cases it causes moderate regrowth. In only a few casesto those men it must seem a sad irony indeedit causes a loss of sex drive and even impotence.

The other irony is that the follicles make the crucial enzyme and thus DHT themselves. "They shoot themselves in the foot," Paus says. Why? That unanswered question is part of a bigger one. One of the most important recent advances in hair biology, Paus says, is the realization that follicles are even more self-regulatory than anyone had imagined. A follicle doesn't just respond to hormones that wash over it through the bloodstream; it makes those hormones itself and presumably uses them for internal conversations. For instance, follicles make the same stress hormones that are made by the hypothalamus in the brain, the pituitary gland, and the adrenal gland. "That's absolutely wild!" Paus says. "That a complex signaling axis involving different organs of the entire body should be installed in all its elements in a miniorgan like the folliclethat's a wild concept."

Hair follicles are us. Not just because they make the stuff we use to display our personalities; they are us in molecular microcosm. "This is the only organ that behaves this way," Bruno Bernard of L'Oréal says, showing off a petri dish in which an individual follicle is thriving in a bath of glucose, vitamins, and amino and fatty acids. "If you take skin or muscle or liver and put it in culture, it falls apart. Studying this little follicle is studying the human beingit's a very simple organ for understanding the big mysteries of biology." That's just one more reason, as if you needed one, to miss it when it's gone.